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dc.contributor.authorNemeth, Zsuzsannaen_US
dc.contributor.authorCsizmadia, Evaen_US
dc.contributor.authorVikstrom, Lisaen_US
dc.contributor.authorLi, Mailinen_US
dc.contributor.authorBisht, Kavitaen_US
dc.contributor.authorFeizi, Alborzen_US
dc.contributor.authorOtterbein, Sherrieen_US
dc.contributor.authorZuckerbraun, Brianen_US
dc.contributor.authorCosta, Daniel B.en_US
dc.contributor.authorPandolfi, Pier Paoloen_US
dc.contributor.authorFillinger, Janosen_US
dc.contributor.authorDöme, Balazsen_US
dc.contributor.authorOtterbein, Leo E.en_US
dc.contributor.authorWegiel, Barbaraen_US
dc.date.accessioned2016-11-18T20:05:26Z
dc.date.issued2016en_US
dc.identifier.citationNemeth, Z., E. Csizmadia, L. Vikstrom, M. Li, K. Bisht, A. Feizi, S. Otterbein, et al. 2016. “Alterations of tumor microenvironment by carbon monoxide impedes lung cancer growth.” Oncotarget 7 (17): 23919-23932. doi:10.18632/oncotarget.8081. http://dx.doi.org/10.18632/oncotarget.8081.en
dc.identifier.issn1949-2553en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29407642
dc.description.abstractWe hypothesized that tumor-associated macrophages (TAMs) are controlled by the diffusible gas carbon monoxide (CO). We demonstrate that induction of apoptosis in lung tumors treated with low doses of CO is associated with increased CD86 expression and activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (Erk) 1/2 pathway in tumor microenvironment. Presence of CD86-positive cells was required for the anti-tumoral effects of CO in established A549 xenografts. We show that the effects of CO on tumor stroma and reprogramming of macrophages towards the anti-tumoral phenotype is mediated by reactive oxygen species (ROS)-dependent activation of MAPK/Erk1/2-c-myc pathway as well as Notch 1-dependent negative feedback on the metabolic enzyme heme oxygenase-1 (HO-1). We find a similar negative correlation between HO-1 and active MAPK-Erk1/2 levels in human lung cancer specimens. In summary, we describe novel non-cell autonomous mechanisms by which the diffusible gas CO dictates changes in the tumor microenvironment through the modulation of macrophages.en
dc.language.isoen_USen
dc.publisherImpact Journals LLCen
dc.relation.isversionofdoi:10.18632/oncotarget.8081en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029674/pdf/en
dash.licenseLAAen_US
dc.subjecttumor microenvironmenten
dc.subjectcarbon monoxideen
dc.subjectmacrophagesen
dc.subjectimmunotherapyen
dc.titleAlterations of tumor microenvironment by carbon monoxide impedes lung cancer growthen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalOncotargeten
dash.depositing.authorCosta, Daniel B.en_US
dc.date.available2016-11-18T20:05:26Z
dc.identifier.doi10.18632/oncotarget.8081*
dash.authorsorderedfalse
dash.contributor.affiliatedWegiel, Barbara
dash.contributor.affiliatedOtterbein, Leo
dash.contributor.affiliatedCosta, Daniel


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